Summary Statements From And Link To “The Diagnosis and Management of Nonalcoholic Fatty Liver Disease: Practice Guidance From the American Association for the Study of Liver Diseases” With An Additional Resource

Here is the PDF link to The Diagnosis and Management of Nonalcoholic Fatty Liver Disease: Practice Guidance From the American Association for the Study of Liver Diseases, HEPATOLOGY, VOL. 67, NO. 1, 2018.

What follows are the Summary Statements from the above [I’ve bolded all the summary statements for quick review]:

Alcohol Consumption and Definition of NAFLD

Guidance Statement:

1. Ongoing or recent alcohol consumption >21 standard drinks on average per week in men and >14 standard drinks on average per week in women is a reasonable threshold for significant alcohol consumption when evaluating patients with suspected NAFLD.

EVALUATION OF INCIDENTALLY DISCOVERED HEPATIC STEATOSIS (HS)

Some patients undergoing thoracic and abdominal
imaging for reasons other than liver symptoms, signs, or abnormal biochemistry may demonstrate unsuspected HS. A recent study showed that 11% of patients with incidentally discovered HS may be at high risk for advanced hepatic fibrosis based on the calculated NAFLD fibrosis score (NFS)*.(71) However, the natural history and optimal diagnostic and management strategies for this patient population have not been investigated.

*Link is to MDCALC

Guidance Statements:

2. Patients with unsuspected HS detected on imaging who have symptoms or signs attributable to liver disease or have abnormal liver chemistries should be evaluated as though they have suspected NAFLD and worked up accordingly.
3. Patients with incidental HS detected on imaging who lack any liver-related symptoms or signs and have normal liver biochemistries should be assessed for metabolic risk factors (e.g., obesity, diabetes mellitus, or dyslipidemia) and alternate causes for HS such as significant alcohol consumption or medications.

Screening for NAFLD in Primary Care, Diabetes, and Obesity Clinics

Guidance Statements:

4. Routine Screening for NAFLD in high-risk
groups attending primary care, diabetes, or obesity clinics is not advised at this time because of uncertainties surrounding diagnostic tests and treatment options, along with lack of knowledge related to long-term benefits and cost-effectiveness of screening.
5. There should be a high index of suspicion for NAFLD and NASH in patients with type 2 diabetes. Clinical decision aids such as NFS* or fibrosis-4 index (FIB-4)* or vibration controlled transient elastography (VCTE) can be used to identify those at low or high risk for advanced fibrosis (bridging fibrosis or cirrhosis).

*Links are to MDCALC

SCREENING OF FAMILY MEMBERS

Guidance Statement:

6. Systematic screening of family members for NAFLD is not recommended currently.

Initial Evaluation of the Patient With Suspected NAFLD

The diagnosis of NAFLD requires that (1) there is
HS by imaging or histology, (2) there is no significant alcohol consumption, (3) there are no competing etiologies for HS, and (4) there are no coexisting causes of CLD.

Common alternative causes of HS are significant
alcohol consumption, hepatitis C, medications, parenteral nutrition, Wilson’s disease (WD), and severe malnutrition (Table 1). When evaluating a patient with newly suspected NAFLD, it is important to exclude coexisting etiologies for CLD, including
hemochromatosis, autoimmune liver disease, chronic viral hepatitis, alpha-1 antitrypsin deficiency, WD, and drug-induced liver injury.

Serological evaluation can uncover laboratory abnormalities in patients with NAFLD that do not always reflect the presence of another liver disease. Two examples of this are elevated serum ferritin and autoimmune antibodies. Mildly elevated serum ferritin is a common feature of NAFLD that does not necessarily indicate hepatic iron overload, though it can impact disease progression. Although the data are somewhat conflicting, serum ferritin >1.5 upper limit of normal (ULN) was associated with more advanced fibrosis in a retrospective cohort of 628 adults.(85) If serum ferritin and transferrin
saturation are elevated in a patient with suspected
NAFLD, genetic hemochromatosis should be excluded. Mutations in the HFE gene occur with variable frequency in patients with NAFLD, and the clinical significance is unclear.(86) Liver biopsy should be considered in the setting of high ferritin and a high iron saturation to determine the presence or extent of hepatic iron accumulation and to exclude significant hepatic injury in a patient with
suspected NAFLD. Low titers of serum autoantibodies, particularly antismooth muscle and antinuclear antibodies, are common in patients with NAFLD and are generally considered to be an epiphenomenon of no clinical consequence, though they often require liver biopsy to exclude autoimmune disease. In a study of 864 well characterized NAFLD subjects from the NASH Clinical Research Network (NASH CRN), significant elevations in serum autoantibodies (antinuclear antibodies >1:160 or antismooth muscle antibodies >1:40) were present in 21% and were not associated with more advanced disease or atypical histological features.(87)

While other diseases are being excluded, history
should be carefully taken for the presence of commonly associated comorbidities, including central obesity, hypertension, dyslipidemia, diabetes or insulin resistance (IR), hypothyroidism, polycystic ovary syndrome, and obstructive sleep apnea.

Guidance Statements:

7. When evaluating a patient with suspected
NAFLD, it is essential to exclude competing etiologies for steatosis and coexisting common CLD.
8. In patients with suspected NAFLD, persistently high serum ferritin, and increased iron saturation, especially in the context of homozygote or heterozygote C282Y HFE mutation, a liver biopsy should be considered.
9. High serum titers of autoantibodies in association with other features suggestive of autoimmune liver disease (>5 ULN aminotransferases, high globulins, or high total protein to albumin ratio) should prompt a work-up for autoimmune liver disease.
10. Initial evaluation of patients with suspected NAFLD should carefully consider the presence of commonly associated comorbidities such as obesity, dyslipidemia, IR or diabetes, hypothyroidism, polycystic ovary syndrome, and sleep apnea.

NONINVASIVE PREDICTION OF STEATOHEPATITIS (SH) IN PATIENTS WITH NAFLD

The presence of MetS is a strong predictor for the
presence of SH in patients with NAFLD.(47,97-100)
Although NAFLD is highly associated with components of MetS, the presence of increasing an number of metabolic diseases, such as IR, type 2 diabetes, hypertension dyslipidemia, and visceral obesity, seems to increase the risk of progressive liver disease.(16,18,41) Therefore, patients with NAFLD and multiple risk factors such as T2DM and hypertension are at the highest risk for adverse outcomes.(20,101) Circulating levels of cytokeratin-18 fragments have been investigated extensively as novel biomarkers for the presence of SH in patients with NAFLD.(47,102,103) This test is currently not available in a clinical care setting.

NONINVASIVE ASSESSMENT OF ADVANCED FIBROSIS IN PATIENTS WITH NAFLD

The commonly investigated noninvasive tools for
the presence of advanced fibrosis in NAFLD include
clinical decision aids (e.g., NAFLD fibrosis score,
FIB-4 index, aspartate aminotransferase [AST] to
platelet ratio index [APRI]), serum biomarkers
(Enhanced Liver Fibrosis [ELF] panel, Fibrometer,
FibroTest, and Hepascore), or imaging (eg, TE, MR
elastography [MRE], acoustic radiation force impulse imaging, and supersonic shear wave elastography).(104)

[For an excellent brief discusssion of each of the above tests please see the Guidance Paper on pp 335 + 336 of the PDF.]

Guidance Statements:

11. In patients with NAFLD, MetS predicts the
presence of SH, and its presence can be used to target patients for a liver biopsy.
12. NFS or FIB-4 index are clinically useful tools for identifying NAFLD patients with higher likelihood of having bridging fibrosis (stage 3) or cirrhosis (stage 4).
13. VCTE or MRE are clinically useful tools for identifying advanced fibrosis in patients with NAFLD.

When to Obtain a Liver Biopsy in Patients With NAFLD

Guidance Statements:

14. Liver biopsy should be considered in patients with NAFLD who are at increased risk of having SH and/or advanced fibrosis.
15. The presence of MetS, NFS or FIB-4, or liver stiffness measured by VCTE or MRE may be used for identifying patients who are at risk for SH and/or advanced fibrosis.
16. Liver biopsy should be considered in patients with suspected NAFLD in whom competing etiologies for HS and the presence and/or severity of coexisting CLDs cannot be excluded without a liver biopsy.

Histopathology of Adult NAFLD

[Please see excellent discussion of the above topic on p 337 of the PDF.]

Guidance Statements:

17. Clinically useful pathology reporting should include a distinction between NAFL (steatosis), NAFL with inflammation, and NASH (steatosis with lobular and portal inflammation and hepatocellular ballooning). A comment on severity (mild, moderate, or severe) may be useful. Specific scoring systems such as NAS(128) and/or SAF(128,129) may be used as deemed appropriate.
18. The presence or absence of fibrosis should be described. If present, a further statement related to location, amount, and parenchymal remodeling is warranted.

Management of Patients With NAFLD

WHOM TO TREAT

The management of NAFLD should consist of
treating liver disease as well as the associated metabolic comorbidities such as obesity, hyperlipidemia, IR, and T2DM. Given that patients with NAFLD without SH or any fibrosis have excellent prognosis from a liver standpoint, pharmacological treatments aimed primarily at improving liver disease should generally be limited to those with biopsy-proven NASH and fibrosis.

Guidance Statement:

19. Pharmacological treatments aimed primarily at improving liver disease should generally be limited to those with biopsy-proven NASH and fibrosis.

LIFESTYLE INTERVENTION

Guidance Statements:

20. Weight loss generally reduces HS, achieved either by hypocaloric diet alone or in conjunction with increased physical activity. A combination of a hypocaloric diet (daily reduction by 500-1,000 kcal) and moderate-intensity exercise is likely to provide the best likelihood of sustaining weight loss over time.
21. Weight loss of at least 3%-5% of body weight
appears necessary to improve steatosis, but a greater weight loss (7%-10%) is needed to improve the majority of the histopathological features of NASH, including fibrosis.
22. Exercise alone in adults with NAFLD may prevent or reduce HS, but its ability to improve other aspects of liver histology remains unknown.

Insulin Sensitizers

METFORMIN

Guidance Statement:

23. Metformin is not recommended for treating NASH in adult patients.

THIAZOLIDINEDIONES

Guidance Statements:

24. Pioglitazone improves liver histology in patients with and without T2DM with biopsy-proven NASH. Therefore, it may be used to treat these patients. Risks and benefits should be discussed with each patient before starting therapy.
25. Until further data support its safety and efficacy, pioglitazone should not be used to treat NAFLD without biopsy-proven NASH.

GLUCAGON-LIKE PEPTIDE-1 ANALOGUES

There has been an interest in investigating the role
of glucagon-like peptide-1 (GLP-1) agonists as therapeutic agents in patients with NAFLD and
NASH.(173-177) In a recently published randomized,
placebo-controlled trial consisting of 52 patients with biopsy-proven NASH, liraglutide administered subcutaneously once-daily for 48 weeks was associated with greater resolution of SH and less progression of fibrosis.(174) As expected, liraglutide was associated with greater weight loss, but also gastrointestinal side effects.

Guidance Statement:

26. It is premature to consider GLP-1 agonists tospecifically treat liver disease in patients with NAFLD or NASH.

VITAMIN E

Guidance Statements:

27. Vitamin E (rrr a-tocopherol) administered at a daily dose of 800 IU/day improves liver histology in nondiabetic adults with biopsy-proven NASH and therefore may be considered for this patient population. Risks and benefits should be discussed with each patient before starting therapy.
28. Until further data supporting its effectiveness become available, vitamin E is not recommended to treat NASH in diabetic patients, NAFLD without liver biopsy, NASH cirrhosis, or cryptogenic cirrhosis.

BARIATRIC SURGERY

NAFLD at all stages is more common in those who
meet criteria for bariatric surgery. Nonsurgical weight loss is effective in improving all histological features of NAFLD, including fibrosis, though most patients had early-stage fibrosis.(136) However, sustained weight loss is difficult to achieve and harder yet to sustain. Bariatric surgery improves or eliminates comorbid disease in most patients and improves long-term survival and death from CVD and malignancy, the two most common causes of death in NAFLD.(192-195)

Guidance Statements:

29. Foregut bariatric surgery can be considered in
otherwise eligible obese individuals with NAFLD or
NASH.
30. It is premature to consider foregut bariatric surgery as an established option to specifically treat NASH.
31. The type, safety, and efficacy of foregut bariatric
surgery in otherwise eligible obese individuals with established cirrhosis attributed to NAFLD are not established. In otherwise eligible patients with compensated NASH or cryptogenic cirrhosis, foregut bariatric surgery may be considered on a case-by-case basis by an experienced bariatric surgery program.

URSODEOXYCHOLIC ACID, OMEGA-3 FATTY ACIDS, AND MISCELLANEOUS AGENTS

Start here p 342 of the PDF.

Additional Resources:

(1) Noninvasive evaluation of nonalcoholic fatty liver disease: Current evidence and practice [PubMed Abstract] [Full Text HTML] [Full Text PDF]. World J Gastroenterol. 2019 Mar 21;25(11):1307-1326. doi: 10.3748/wjg.v25.i11.1307.

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